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Mi-iron - Moderately Increased Iron - is Reducing Iron Overload Necessary? (Mi-iron)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01631708
Recruitment Status : Completed
First Posted : June 29, 2012
Last Update Posted : September 27, 2016
Sponsor:
Collaborators:
Austin Health
Royal Brisbane and Women's Hospital
Fremantle Hospital and Health Service
Melbourne Health
The University of Queensland
Information provided by (Responsible Party):
Martin Delatycki, Murdoch Childrens Research Institute

Tracking Information
First Submitted Date  ICMJE June 24, 2012
First Posted Date  ICMJE June 29, 2012
Last Update Posted Date September 27, 2016
Study Start Date  ICMJE June 2012
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2012)
Fatigue [ Time Frame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have approximately 6 third weekly treatments however this will vary depending on initial SF. ]
Modified Fatigue Impact Scale (MFIS). The MFIS is a shortened version of the Fatigue Impact Scale. This 21-item scale can be self completed and measures the impact of fatigue on physical, cognitive and psychosocial functioning. Each item is scored from 0 (never) to 4 (almost always) resulting in a score from 0-84. In addition, physical (0-36), cognitive (0-40) and psychosocial (0-8) subscale scores can be derived.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01631708 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2012)
  • Change in markers of liver fibrosis [ Time Frame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks). ]
    Liver fibrosis will be assessed using Hepascore and Fibrometer (blood tests) and transient elastography (ultrasound).
  • Quality of life [ Time Frame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks). ]
    Medical Outcomes Study 36-item short form (SF36). As there are no specific quality of life tools available for HH, we will use this very widely used generic tool that has been used in a number of HH studies. This tool covers eight dimensions of health and wellbeing. One study found that individuals seen in a HH clinic and who had no clinical symptoms had significantly lower scores on a number of dimensions of the SF36 compared to population norms.
  • Depression and Anxiety [ Time Frame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks). ]
    The Hospital Anxiety and Depression Scale (HADS) is a brief self-report measure designed to screen for anxiety symptoms and depression symptoms in a hospital setting. It is composed of two seven-item subscales, the Anxiety (HADS-A) and Depression (HADS-D) subscales, and a 14-item total scale (HADS-T). Participants use a four-point Likert-type scale to rate how they have felt in the past week. It has been found to be valid and reliable in various populations.
  • Arthritis [ Time Frame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks). ]
    The presence and impact of arthritis will be measured by the Arthritis Impact Measurement Scales 2 short form. This is a 24 item validated scale that assesses the impact of arthritis on the individual over the past four weeks. We will also ascertain the use of arthritis medication at baseline and end of erythrocytapheresis/sham erythrocytapheresis.
  • Markers of oxidative stress [ Time Frame: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks). ]
    To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mi-iron - Moderately Increased Iron - is Reducing Iron Overload Necessary?
Official Title  ICMJE Mi-Iron - Moderately Increased Iron - is Reducing Iron Overload Necessary?
Brief Summary Haemochromatosis is a preventable genetic iron overload disorder. Untreated, it can shorten life due mainly to liver cirrhosis and cancer. It can be prevented by blood donation to maintain normal iron levels. It is unclear, however, whether treatment is necessary when individuals have moderate elevation of iron in the body. This research project will study the effects of treatment in this group by assessing a number of scans, questionnaires and blood tests in treated and untreated individuals.
Detailed Description There is mounting evidence that treatment of moderate iron overload in HFE related hereditary haemochromatosis (HH) is not necessary. This project aims to undertake a randomised patient-blinded trial of erythrocytapheresis compared to sham erythrocytapheresis (using plasmapheresis) in individuals who have serum ferritin (SF) above the upper limit of the normal range but < 1000ug/L (defined here as moderate iron overload) due to HFE mutations and to compare the prevalence of symptoms and objective markers of disease in the two treatment arms.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Hereditary Haemochromatosis
Intervention  ICMJE
  • Procedure: Erythrocytapheresis

    To achieve a blinded randomised trial, apheresis treatment will be used. Those in arm 1 will have erythrocytapheresis reducing iron levels and those in arm 2 will have plasmapheresis and their iron levels will not be reduced.

    An apheresis machine will be used to remove red blood cells only from the erythrocytapheresis group. Subjects will have third weekly treatments until SF levels are reduced to ~100 ug/L in accordance with current guidelines.

    Other Name: red blood cell removal, red blood cell apheresis
  • Procedure: Plasmapheresis
    An apheresis machine will be used to remove blood plasma only from the plasmapheresis group. Those in arm 2 will have the approximate number of episodes of apheresis that would be required to reduce their SF to normal had they been randomised to the true treatment arm. Those in the sham arm will be offered to have venesection at their choice of venue or to have their SF normalised by erythrocytapheresis after the initial blinded part of the study. This will be done because it will not be known for some time if there is benefit from normalisation of SF and therefore leaving people with elevated SF that may be harmful.
    Other Name: plasma removal, sham erythrocytapheresis
Study Arms  ICMJE
  • Active Comparator: Erythrocytapheresis

    Erythrocytapheresis is a procedure whereby whole blood is drawn from an individual and all elements except erythrocytes are returned to the donor. An automated filtration process removes the erythrocytes.

    Those in arm 1 will have third weekly erythrocytapheresis until their SF is returned to the normal range.

    Intervention: Procedure: Erythrocytapheresis
  • Sham Comparator: Plasmapheresis

    In plasmapheresis, the plasma is removed by the automated filtration process whilst other blood elements including erythrocytes are returned to the subject.

    Those in arm 2 will have plasmapheresis with the approximate number of episodes of apheresis that would be required to reduce their SF to normal had they been randomised to the true treatment arm.

    Intervention: Procedure: Plasmapheresis
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 9, 2015)
100
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2012)
110
Actual Study Completion Date  ICMJE July 2016
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. HFE C282Y homozygous.
  2. Aged 18 - 70 years .
  3. SF above the upper limit of the normal range of 300µg/L but less than 1000µg/L with a currently or previously raised TS (>greater than the upper limit of normal for the testing laboratory).

Exclusion Criteria:

  1. HH due to genotypes other than HFE C282Y homozygosity.
  2. Normal SF, SF > 1000µg/L.
  3. Other major risk factor(s) for liver toxicity or other significant co-morbidities including positivity for hepatitis B or C, excess alcohol consumption (> 60g/day in males and 40g/day in females) or body mass index > 35.
  4. Has had venesection therapy for HH in the last two years.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01631708
Other Study ID Numbers  ICMJE 04609
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Martin Delatycki, Murdoch Childrens Research Institute
Study Sponsor  ICMJE Murdoch Childrens Research Institute
Collaborators  ICMJE
  • Austin Health
  • Royal Brisbane and Women's Hospital
  • Fremantle Hospital and Health Service
  • Melbourne Health
  • The University of Queensland
Investigators  ICMJE
Principal Investigator: Martin B Delatycki Austin Health/Murdoch Childrens Research Institute
PRS Account Murdoch Childrens Research Institute
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP